Helicobacter pylori, a bacterium that infects the stomach, is related to a form of low grade, B cell, non-Hodgkin's lymphoma described as mucosa- associated lymphoid tissue (MALT) lymphoma. Recent studies indicate that antibiotic treatment of H. pylori infection can cause the regression of MALT lymphoma in some patients. These clinical observations are supported by preliminary laboratory findings that tumor B cell proliferation in MALT lymphoma may be dependent on growth stimuli, such as cytokine growth factors, produced by H. pylori-induced immune accessory (inflammatory) cells present in the MALT lesion. Withdrawal of the proliferative stimulus by eradication of H. pylori is postulated to cause tumor cell death and tumor regression. These findings raise a number of important questions regarding: i) the nature of the malignant lymphoid cells in the MALT lymphoma lesion; ii) the role of the inflammatory response to H. pylori, in driving or sustaining the neoplastic (MALT lymphoma) cells; and iii) the relationship of H. pylori to the immune accessory cells and the possible role of H pylori in inducing the production of growth and differentiation factors required by MALT lymphoma. The proposed laboratory experiments are designed to address these questions by defining: 1) the nature and biology of the MALT lymphoma cells; 2) the response of MALT lymphoma cells to specific B cell growth stimulating cytokines (e.g.IL14, other BCGFs and Interleukins) and co-stimulatory factors for B cells (e.g. CD40 ligand, gp39); 3) the role of H pylori in generating and sustaining the lesions in which MALT lymphomas arise; and 4) the potential therapeutic effects of depriving the lymphoma cells of the cytokine-rich milieu generated by the HP-induced inflammatory response. A clinical trial of antibiotic treatment of patients with MALT lymphoma, conducted in parallel to the in-vitro experiments, will provide the appropriate tissue specimens as well as the opportunity for clinical and laboratory correlations. These studies may contribute to understanding the pathophysiology of MALT lymphoma in relation to H. pylori, as well as provide insights into therapeutic strategies for these patients.